The prevalence of HIV infection worldwide is greater than 40 million people; in the United States, over 1 million people are infected. HIV-associated neurocognitive disorders (HAND)—progressing in disability from asymptomatic neurocognitive impairment (ANI) to HIV-associated mild neurocognitive disorder (MND) to HIV-associated dementia (HAD)—has been recognized as common sequelae of infection. Early in the epidemic, more than 50% of all HIV-positive patients were diagnosed with HAD.
Thanks to the advent of antiretroviral therapy, human immunodeficiency virus (HIV)-infected individuals have significantly reduced mortality and morbidity. The prevalence of HAD has greatly diminished while less severe ANI and MND have risen as individuals live longer with the disease. However, HIV-infected individuals are dependent on the use of antiretroviral drugs to suppress HIV replication for the remainder of their lives. Several studies showed that nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors induce overproduction of reactive oxygen species (ROS) associated with devastating side effects to the heart, liver, and central nervous system.
Also, emerging evidence indicates that persistence of HIV in patients treated with antiretroviral therapy and possibly the antiretroviral therapy itself contribute to cognitive decline such as seen in HAND as the HIV-infected population ages.
There is therefore a need in the art for adjunctive neuroprotective therapy in addition to antiretroviral therapy for treatment of cognitive decline as the HIV-infected individuals. Also, there is a need to inhibit viral infection or viral entry in to a cell.
Dietary flaxseed (FS) is a nutritional whole grain with high contents of omega-3 fatty acids and lignans. Flaxseed is the richest source of the lignan secoisolariciresinol diglucoside (SDG). After ingestion, secoisolariciresinol diglucoside (SDG) is converted to secoisolariciresinol, which is further metabolized by intestinal bacteria to the mammalian lignans enterodiol and enterolactone. Clinical studies using dietary SDG stress its safety and tolerability and showed that a dose of at least 500 mg SDG/day for approximately 8 weeks has a positive effect on cardiovascular risk factors in humans. Flaxseed can be safely consumed in adequate quantities to induce the anti-oxidant response pathway and to exert anti-inflammatory and free radical scavenging properties via the action of its polyphenolic lignan component, secoisolariciresinol diglucoside (SDG).
A growing body of evidence indicates that SDG metabolites may provide cardiovascular (CV) and anti-cancer benefits due to their weak oestrogenic or anti-oestrogenic effects, antioxidant activity, ability to induce phase 2 proteins and/or inhibit the activity of certain enzymes, or by other as yet unidentified mechanisms. SDG metabolites may protect against CV disease and the metabolic syndrome by reducing lipid and glucose concentrations, lowering blood pressure, and decreasing oxidative stress and inflammation. Flax lignans may also reduce cancer risk by preventing pre-cancerous cellular changes and by reducing angiogenesis and metastasis. Moreover, FS and SDG are protective in lungs against hyperoxia, acid aspiration, lipopolysaccharide-induced acute lung injury, warm lung ischemia/reperfusion injury and pneumonitis, resulting from thoracic radiation.